Jan. 13, 2023
In this Q&A, Samir Babayev, M.D., a reproductive endocrinologist at Mayo Clinic, responds to questions about ovarian tissue cryopreservation and autotransplantation and services offered at Mayo Clinic in Minnesota.
What has changed at Mayo Clinic for ovarian tissue preservation and autotransplant?
The age range for ovarian cryopreservation has evolved at Mayo Clinic's Minnesota campus. We also are now ready to start autotransplant of cryopreserved ovaries.
Mayo Clinic has a long history of performing ovarian cryopreservation for pediatric patients whose cancer treatment is expected to affect their fertility. This service has been led by Asma J. Chattha, M.B.B.S., a pediatric gynecologist at Mayo Clinic's Minnesota campus.
In addition to providing this service to children, we now serve many adult patients with cancer or cancer-like conditions.
When I started at Mayo Clinic in 2019, I brought with me knowledge of autotransplant for cryopreserved ovarian tissue. I trained at New York Medical College under Kutluk Oktay, M.D., Ph.D., now at Yale School of Medicine, who pioneered cryopreserved ovarian transplant.
What has changed in the field of reproductive medicine for ovarian tissue cryopreservation and autotransplantation?
There have been significant changes. In 2019, the Practice Committee of the American Society for Reproductive Medicine proclaimed that ovarian tissue cryopreservation and autotransplant should no longer be considered experimental. Instead, the committee declared that these procedures should be considered standard of care. This shift expedites the process for patients, as Institutional Review Board approval is no longer needed. Removal of the experimental label also helps with payer coverage for these procedures.
Who is eligible for these procedures?
Candidates include prepubertal girls through adult women who have not gone through menopause and require urgent treatment for cancer or cancer-like conditions. In these cases, the patient cannot pause treatment for ovarian stimulation and oocyte freezing. The targeted, high-dose chemotherapy used prior to treatments such as bone marrow transplant will kill off the patient's eggs. For these patients — and for patients with diseases such as intracranial tumors or advanced breast cancer — the only fertility option is to freeze ovarian tissue. The tissue remains frozen until the patient completes therapy and is ready to have children. The patient also needs to be cured of the disease and healthy before transplant.
What is the procedure for ovarian tissue cryopreservation?
We remove only one ovary to provide for the possibility of natural hormonal function restoration, which does happen occasionally. Before cryopreservation, the ovarian tissue is divided into smaller pieces. This decreases volume and allows better penetration of the antifreeze we use to extract water from the cells, deflating them and preventing damage.
We previously used a slow ovarian tissue freezing method at Mayo Clinic. Now we do flash freezing, immediately freezing the tissue to 170 degrees Fahrenheit below zero. We use this method as it allows freezing before the antifreeze can affect the cells, but we do not do so to the point of freeze-drying. Some reproductive endocrinologists still do slow freezing for ovarian tissue. However, the field is moving in favor of flash freezing.
We often combine ovary removal for cryopreservation with other procedures such as chemotherapy port installation to reduce the number of procedures and sedations a patient needs to undergo.
Is there anything notable that has changed as autotransplantation has evolved?
Yes. One notable aspect has been the anatomical location of the autotransplant. The early autotransplants were performed heterotopically — outside of the usual location for an ovary — such as in the forearm. The reason for this is that if the ovarian tissue was transplanted into the same place from which it was removed, it would be difficult to tell if the transplant worked, rather than an awakening of the remaining ovary that was not removed. Next, reproductive endocrinologists performed autotransplants on the opposite side from the removed ovary, for the same purpose. From a purely practical perspective, if the patient decides to pursue in vitro fertilization (IVF), that process is easier with a heterotopic transplant. Now that reproductive endocrinologists have seen that orthotopic ovarian transplant works well, heterotopic transplant is less common. The surgeon usually performs an orthotopic transplant at the site of the previous ovary or right below it.
It is also notable that once the ovarian tissue is put back into the patient, the main portion of the tissue dies until revascularization. It is not a quick process.
Do most patients and their physicians plan for natural birth or IVF after transplant?
In a study of hundreds of patients' ovarian transplants and more than 200 pregnancies published in a 2019 issue of Fertility and Sterility, more than half resulted in natural conception. Up to two-thirds of women who have ovarian transplant prefer the natural conception route.
Is there any downside to a patient pursuing natural pregnancy after transplant?
Yes, there is. The issue is the longevity of the tissue transplanted. As mentioned, much of the tissue dies. The longevity of the remaining tissue is less than three years, on average. Natural conception is not as efficient as IVF.
Is IVF post-transplant the same as for someone who did not undergo ovarian tissue transplant?
No, IVF is different after ovarian transplant, such as:
- Tissue pressure is much higher.
- Follicles are smaller.
- The egg collection process is different.
- Peak estrogen levels are different.
Do most women who undergo ovarian cryopreservation return for transplant?
One-third come back for transplantation.
Are many medical centers doing cryopreservation and ovarian tissue autotransplantation?
Approximately 20 medical centers perform ovarian tissue cryopreservation in the U.S., according to the Oncofertility Consortium. However, only a handful of centers offer ovarian tissue transplant in the U.S.
If a patient underwent ovarian tissue cryopreservation at one medical center and would like to have ovarian tissue transplant elsewhere, is that possible?
Yes, it is possible. For example, here at Mayo Clinic's campus in Minnesota, we would be happy to arrange for a specialized shipment of a patient's cryopreserved ovarian tissue for autotransplant at our medical center.
Are you accepting referrals for ovarian tissue cryopreservation and transplant?
Absolutely.
For more information
Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertility and Sterility. 2019;112:1022.
Andersen ST, et al. Ovarian stimulation and assisted reproductive technology outcomes in women transplanted with cryopreserved ovarian tissue: A systematic review. Fertility and Sterility. 2019;112:908.
Clinic finder. The Oncofertility Consortium.
Obstetrics and Gynecology Referrals.
Refer a patient to Mayo Clinic.